DEPO MEDRONE INJECTION 40 MG/ML

Active substance: METHYLPREDNISOLONE ACETATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Depo-Medrone 40 mg/ml.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Methylprednisolone Acetate BP 40 mg/ml.

3

PHARMACEUTICAL FORM
Sterile, aqueous suspension.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Depo-Medrone may be used locally or systemically, particularly where oral
therapy is not feasible.
Depo-Medrone may be used by any of the following routes: intramuscular,
intra-articular, periarticular, intrabursal, intralesional or into the tendon sheath.
It must not be used by the intrathecal or intravenous routes (see Contraindications and Undesirable effects).
Intramuscular administration:
1.

Rheumatic disorders
Rheumatoid arthritis

2.

Collagen diseases/arteritis
Systemic lupus erythematosus

3.

Dermatological diseases
Severe erythema multiforme (Stevens-Johnson syndrome)

4.

Allergic states
Bronchial asthma
Severe seasonal and perennial allergic rhinitis
Drug hypersensitivity reactions
Angioneurotic oedema

5.

Gastro-intestinal diseases
Ulcerative colitis
Crohn's disease

6.

Respiratory diseases
Fulminating or disseminated tuberculosis (with appropriate antituberculous
chemotherapy)
Aspiration of gastric contents

7.

Miscellaneous
TB meningitis (with appropriate antituberculous chemotherapy)

Intra-articular administration:
Rheumatoid arthritis
Osteo-arthritis with an inflammatory component
Soft tissue administration (intrabursal, periarticular, into tendon sheath):
Synovitis not associated with infection
Epicondylitis
Tenosynovitis
Plantar fasciitis
Bursitis
Intralesional:
Keloids
Localized lichen planus
Localized lichen simplex
Granuloma annulare
Discoid lupus erythematosus
Alopecia areata

4.2

Posology and method of administration
Depo-Medrone should not be mixed with any other suspending agent or
solution. Parenteral drug products should be inspected visually for particulate
matter and discoloration prior to administration, whenever suspension and
container permit. Depo-Medrone may be used by any of the following routes:
intramuscular, intra-articular, periarticular, intrabursal, intralesional and into
the tendon sheath. It must not be used by the intrathecal or intravenous routes
(see Contra-indications and Undesirable effects).
Undesirable effects may be minimised by using the lowest effective dose for
the minimum period (see Special warnings and special precautions for use).
Depo-Medrone vials are intended for single dose use only.
Intramuscular - for sustained systemic effect: Allergic conditions (severe
seasonal and perennial allergic rhinitis, asthma, drug reactions), 80 - 120 mg
(2 - 3 ml).

Dermatological conditions, 40 - 120 mg (1 - 3 ml).
Rheumatic disorders and collagen diseases (rheumatoid arthritis, SLE), 40 120 mg (1 - 3 ml) per week.
Dosage must be individualized and depends on the condition being treated and
its severity.
Note: Depo-Medrone is not intended for the prophylaxis of severe seasonal
and perennial allergic rhinitis or other seasonal allergies and should be
administered only when symptoms are present.
The frequency of intramuscular injections should be determined by the
duration of clinical response.
In the case of seasonal allergic rhinitis a single injection is frequently
sufficient. If necessary, however, a second injection may be given after two to
three weeks.
On average the effect of a single 2 ml (80 mg) injection may be expected to
last approximately two weeks.
Intra-articular: Rheumatoid arthritis, osteo-arthritis. The dose of DepoMedrone depends upon the size of the joint and the severity of the condition.
Repeated injections, if needed, may be given at intervals of one to five or more
weeks depending upon the degree of relief obtained from the initial injection.
A suggested dosage guide is: large joint (knee, ankle, shoulder), 20 - 80 mg
(0.5 - 2 ml); medium joint (elbow, wrist), 10 - 40 mg (0.25 - 1 ml); small joint
(metacarpophalangeal, interphalangeal, sternoclavicular, acromioclavicular), 4
- 10 mg (0.1 - 0.25 ml).
Intrabursal: Subdeltoid bursitis, prepatellar bursitis, olecranon bursitis. For
administration directly into bursae, 4 - 30 mg (0.1 - 0.75 ml). In most cases,
repeat injections are not needed.
Intralesional: Keloids, localised lichen planus, localized lichen simplex,
granuloma annulare, alopecia areata, and discoid lupus erythematosus. For
administration directly into the lesion for local effect in dermatological
conditions, 20 - 60 mg (0.5 - 1.5 ml). For large lesions, the dose may be
distributed by repeated local injections of 20 - 40 mg (0.5 - 1 ml). One to four
injections are usually employed. Care should be taken to avoid injection of
sufficient material to cause blanching, since this may be followed by a small
slough.
Peri-articular: Epicondylitis. Infiltrate 4 - 30 mg (0.1 - 0.75 ml) into the
affected area.

Into the tendon sheath: Tenosynovitis, epicondylitis. For administration
directly into the tendon sheath, 4 - 30 mg (0.1 - 0.75 ml). In recurrent or
chronic conditions, repeat injections may be necessary.
Special precautions should be observed when administering Depo-Medrone.
Intramuscular injections should be made deeply into the gluteal muscles. The
usual technique of aspirating prior to injection should be employed to avoid
intravascular administration. Doses recommended for intramuscular injection
must not be administered superficially or subcutaneously.
Intra-articular injections should be made using precise, anatomical localisation
into the synovial space of the joint involved. The injection site for each joint
is determined by that location where the synovial cavity is most superficial
and most free of large vessels and nerves. Suitable sites for intra-articular
injection are the knee, ankle, wrist, elbow, shoulder, phalangeal and hip joints.
The spinal joints, unstable joints and those devoid of synovial space are not
suitable. Treatment failures are most frequently the result of failure to enter
the joint space. Intra-articular injections should be made with care as follows:
ensure correct positioning of the needle into the synovial space and aspirate a
few drops of joint fluid. The aspirating syringe should then be replaced by
another containing Depo-Medrone. To ensure position of the needle, synovial
fluid should be aspirated and the injection made. After injection the joint is
moved slightly to aid mixing of the synovial fluid and the suspension.
Subsequent to therapy care should be taken for the patient not to overuse the
joint in which benefit has been obtained. Negligence in this matter may permit
an increase in joint deterioration that will more than offset the beneficial
effects of the steroid.
Intrabursal injections should be made as follows: the area around the injection
site is prepared in a sterile way and a wheal at the site made with 1 per cent
procaine hydrochloride solution. A 20 to 24 gauge needle attached to a dry
syringe is inserted into the bursa and the fluid aspirated. The needle is left in
place and the aspirating syringe changed for a small syringe containing the
desired dose. After injection, the needle is withdrawn and a small dressing
applied. In the treatment of tenosynovitis care should be taken to inject DepoMedrone into the tendon sheath rather than into the substance of the tendon.
Due to the absence of a true tendon sheath, the Achilles tendon should not be
injected with Depo-Medrone.
Children: Dosage may be reduced for infants and children but should be
governed more by the severity of the condition and response of the patient,
than by age or size.
Elderly patients: When used according to instructions, there is no information
to suggest that a change in dosage is warranted in the elderly. However,
treatment of elderly patients, particularly if long-term, should be planned
bearing in mind the more serious consequences of the common side-effects of
corticosteroids in old age and close clinical supervision is required (see
Special warnings and special precautions for use).

4.3

Contraindications
Depo-medrone is contra-indicated where there is known hypersensitivity to
components and in systemic infection unless specific anti-infective therapy is
employed.
Due to its potential for neurotoxicity, Depo-Medrone must not be given by the
intrathecal route. In addition, as the product is a suspension it must not be
given by the intravenous route (see Undesirable effects).

4.4

Special warnings and precautions for use
Warnings and Precautions:
1.
A Patient Information Leaflet is provided in the pack by the
manufacturer.
2.

Undesirable effects may be minimised by using the lowest effective
dose for the minimum period. Frequent patient review is required to
appropriately titrate the dose against disease activity (see Posology and
method of administration).

3.

Patients should carry 'Steroid Treatment' cards which give clear
guidance on the precautions to be taken to minimise risk and which
provide details of prescriber, drug, dosage and the duration of
treatment.

4.

Depo-Medrone vials are intended for single dose use only.
multidose use of the product may lead to contamination.

5.

Depo-Medrone is not recommended for epidural, intranasal, intraocular, or any other unapproved route of administration. See
Undesirable effects section for details of side-effects reported from
some non-recommended routes of administration.

6.

Due to the absence of a true tendon sheath, the Achilles tendon should
not be injected with Depo-Medrone.

7.

While crystals of adrenal steroids in the dermis suppress inflammatory
reactions, their presence may cause disintegration of the cellular
elements and physiochemical changes in the ground substance of the
connective tissue. The resultant infrequently occurring dermal and/or
subdermal changes may form depressions in the skin at the injection
site. The degree to which this reaction occurs will vary with the
amount of adrenal steroid injected. Regeneration is usually complete
within a few months or after all crystals of the adrenal steroid have
been absorbed. In order to minimize the incidence of dermal and
subdermal atrophy, care must be exercised not to exceed recommended
doses in injections. Multiple small injections into the area of the lesion

Any

should be made whenever possible. The technique of intra-articular
and intramuscular injection should include precautions against
injection or leakage into the dermis. Injection into the deltoid muscle
should be avoided because of a high incidence of subcutaneous
atrophy.
8.

Intralesional doses should not be placed too superficially, particularly
in easily visible sites in patients with deeply pigmented skins, since
there have been rare reports of subcutaneous atrophy and
depigmentation.

9.

Systemic absorption of methylprednisolone occurs following
intra-articular injection of Depo-Medrone. Systemic as well as local
effects can therefore be expected.

10.

Intra-articular corticosteroids are associated with a substantially
increased risk of inflammatory response in the joint, particularly
bacterial infection introduced with the injection.
Charcot-like
arthropathies have been reported particularly after repeated injections.
Appropriate examination of any joint fluid present is necessary to
exclude any bacterial infection, prior to injection.

11.

Following a single dose of Depo-Medrone, plasma cortisol levels are
reduced and there is evidence of hypothalamic-pituitary-adrenal (HPA)
axis suppression. This suppression lasts for a variable period of up to 4
weeks. The usual dynamic tests of HPA axis function can be used to
diagnose evidence of impaired activity (e.g. Synacthen test).

12.

Adrenal cortical atrophy develops during prolonged therapy and may
persist for months after stopping treatment. In patients who have
received more than physiological doses of systemic corticosteroids
(approximately 6 mg methylprednisolone) for greater than 3 weeks,
withdrawal should not be abrupt. How dose reduction should be
carried out depends largely on whether the disease is likely to relapse
as the dose of systemic corticosteroids is reduced. Clinical assessment
of disease activity may be needed during withdrawal. If the disease is
unlikely to relapse on withdrawal of systemic corticosteroids, but there
is uncertainty about HPA suppression, the dose of systemic
corticosteroid may be reduced rapidly to physiological doses. Once a
daily dose of 6 mg methylprednisolone is reached, dose reduction
should be slower to allow the HPA-axis to recover.
Abrupt withdrawal of systemic corticosteroid treatment, which has
continued up to 3 weeks is appropriate if it considered that the disease
is unlikely to relapse. Abrupt withdrawal of doses up to 32 mg daily of
methylprednisolone for 3 weeks is unlikely to lead to clinically
relevant HPA-axis suppression, in the majority of patients. In the
following patient groups, gradual withdrawal of systemic
corticosteroid therapy should be considered even after courses lasting 3
weeks or less:

• Patients who have had repeated courses of systemic corticosteroids,
particularly if taken for greater than 3 weeks.
• When a short course has been prescribed within one year of
cessation of long-term therapy (months or years).
• Patients who may have reasons for adrenocortical insufficiency
other than exogenous corticosteroid therapy.
• Patients receiving doses of systemic corticosteroid greater than 32
mg daily of methylprednisolone.
• Patients repeatedly taking doses in the evening.
13.

Since mineralocorticoid secretion may be impaired, salt and/or a
mineralocorticoid should be administered concurrently.

14.

Because rare instances of anaphylactic reactions have occurred in
patients receiving parenteral corticosteroid therapy, appropriate
precautionary measures should be taken prior to administration,
especially when the patient has a history of drug allergy.

15.

Corticosteroids may mask some signs of infection, and new infections
may appear during their use. Suppression of the inflammatory
response and immune function increases the susceptibility to fungal,
viral and bacterial infections and their severity.
The clinical
presentation may often be atypical and may reach an advanced stage
before being recognised.

16.

Chickenpox is of serious concern since this normally minor illness may
be fatal in immunosuppressed patients. Patients (or parents of
children) without a definite history of chickenpox should be advised to
avoid close personal contact with chickenpox or herpes zoster and if
exposed they should seek urgent medical attention.
Passive
immunization with varicella/zoster immunoglobin (VZIG) is needed by
exposed non-immune patients who are receiving systemic
corticosteroids or who have used them within the previous 3 months;
this should be given within 10 days of exposure to chickenpox. If a
diagnosis of chickenpox is confirmed, the illness warrants specialist
care and urgent treatment. Corticosteroids should not be stopped and
the dose may need to be increased.

17.

Live vaccines should not be given to individuals with impaired
immune responsiveness. The antibody response to other vaccines may
be diminished.

18.

The use of Depo-Medrone in active tuberculosis should be restricted to
those cases of fulminating or disseminated tuberculosis in which the
corticosteroid is used for the management of the disease in conjunction
with an appropriate antituberculous regimen. If corticosteroids are
indicated in patients with latent tuberculosis or tuberculin reactivity,
close observation is necessary as reactivation of the disease may occur.
During prolonged corticosteroid therapy, these patients should receive
chemoprophylaxis.

19.

Care should be taken for patients receiving cardioactive drugs such as
digoxin because of steroid induced electrolyte disturbance/potassium
loss (see Undesirable effects).

20.

The following precautions apply for parenteral corticosteroids:
Following intra-articular injection, the occurrence of a marked increase
in pain accompanied by local swelling, further restriction of joint
motion, fever, and malaise are suggestive of septic arthritis. If this
complication occurs and the diagnosis of sepsis is confirmed,
appropriate antimicrobial therapy should be instituted.
Local injection of a steroid into a previously infected joint is to be
avoided.
Corticosteroids should not be injected into unstable joints.
Sterile technique is necessary to prevent infections or contamination.
The slower rate of absorption by intramuscular administration should
be recognised.

Special precautions:
Particular care is required when considering the use of systemic
corticosteroids in patients with the following conditions and frequent patient
monitoring is necessary.
1.

Osteoporosis (post-menopausal females are particularly at risk).

2.

Hypertension or congestive heart failure.

3.

Existing or previous history of severe affective disorders (especially
previous steroid psychosis).

4.

Diabetes mellitus (or a family history of diabetes).

5.

History of tuberculosis.

6.

Glaucoma (or a family history of glaucoma).

7.

Previous corticosteroid-induced myopathy.

8.

Liver failure or cirrhosis.

9.

Renal insufficiency.

10.

Epilepsy.

11.

Peptic ulceration.

12.

Fresh intestinal anastomoses.

13.

Predisposition to thrombophlebitis.

14.

Abscess or other pyogenic infections.

15.

Ulcerative colitis.

16.

Diverticulitis.

17.

Myasthenia gravis.

18.

Ocular herpes simplex, for fear of corneal perforation.

19.

Hypothyroidism.

20.

Patients and/or carers should be warned that potentially severe
psychiatric adverse reactions may occur with systemic steroids (see
section 4.8). Symptoms typically emerge within a few days or weeks of
starting treatment. Risks may be higher with high doses/systemic
exposure (see also section 4.5 Interaction with Other Medicaments and
Other Forms of Interaction that can increase the risk of side effects),
although dose levels do not allow prediction of the onset, type, severity
or duration of reactions. Most reactions recover after either dose
reduction or withdrawal, although specific treatment may be necessary.
Patients/carers should be encouraged to seek medical advice if
worrying psychological symptoms develop, especially if depressed
mood or suicidal ideation is suspected. Patients/carers should be alert
to possible psychiatric disturbances that may occur either during or
immediately after dose tapering/withdrawal of systemic steroids,
although such reactions have been reported infrequently.
Particular care is required when considering the use of systemic
corticosteroids in patients with existing or previous history of severe
affective disorders in themselves or in their first degree relatives. These
would include depressive or manic-depressive illness and previous
steroid psychosis.

Use in Children: Corticosteroids cause growth retardation in infancy,
childhood and adolescence which may be irreversible. Treatment should be
limited to the minimum dosage for the shortest possible time.
Use in the elderly: The common adverse effects of systemic corticosteroids
may be associated with more serious consequences in old age, especially
osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection
and thinning of the skin. Close clinical supervision is required to avoid lifethreatening reactions.

4.5

Interaction with other medicinal products and other forms of interaction
1.

2.

Drugs that induce hepatic enzymes, such as rifampicin, rifabutin, carbamazepine,
phenobarbitone, phenytoin, primidone, and aminoglutethimide enhance the metabolism of
corticosteroids and its therapeutic effects may be reduced.

3.

Drugs such as erythromycin and ketoconazole may inhibit the metabolism of
corticosteroids and thus decrease their clearance.

4.

Steroids may reduce the effects of anticholinesterases in myasthenia gravis. The
desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and
diuretics are antagonised by corticosteroids, and the hypokalaemic effects of
acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced.

5.

The efficacy of coumarin anticoagulants may be enhanced by concurrent
corticosteroid therapy and close monitoring of the INR or prothrombin time is
required to avoid spontaneous bleeding.

6.

The renal clearance of salicylates is increased by corticosteroids and steroid
withdrawal may result in salicylate intoxication. Salicylates and non-steroidal antiinflammatory agents should be used cautiously in conjunction with corticosteroids in
hypothrombinaemia.

7.

4.6

Convulsions have been reported with concurrent use of methylprednisolone and
cyclosporin. Since concurrent administration of these agents results in a mutual
inhibition of metabolism, it is possible that convulsions and other adverse effects
associated with the individual use of either drug may be more apt to occur.

Steroids have been reported to interact with neuromuscular blocking agents such as
pancuronium with partial reversal of the neuromuscular block.

Fertility, Pregnancy and lactation
Pregnancy
The ability of corticosteroids to cross the placenta varies between individual
drugs, however, methylprednisolone does cross the placenta.
Administration of corticosteroids to pregnant animals can cause abnormalities
of foetal development including cleft palate, intra-uterine growth retardation
and affects on brain growth and development. There is no evidence that
corticosteroids result in an increased incidence of congenital abnormalities,
such as cleft palate in man, however, when administered for long periods or
repeatedly during pregnancy, corticosteroids may increase the risk of intrauterine growth retardation. Hypoadrenalism may, in theory , occur in the
neonate following prenatal exposure to corticosteroids but usually resolves
spontaneously following birth and is rarely clinically important. As with all
drugs, corticosteroids should only be prescribed when the benefits to the
mother and child outweigh the risks. When corticosteroids are essential,

however, patients with normal pregnancies may be treated as though they were
in the non-gravid state.
Lactation
Corticosteroids are excreted in small amounts in breast milk, however, doses
of up to 40 mg daily of methylprednisolone are unlikely to cause systemic
effects in the infant. Infants of mothers taking higher doses than this may have
a degree of adrenal suppression, but the benefits of breastfeeding are likely to
outweigh any theoretical risk.

4.7

Effects on ability to drive and use machines
None stated.

4.8

Undesirable effects
The incidence of predictable undesirable side-effects associated with the use
of corticosteroids, including hypothalamic-pituitary-adrenal suppression
correlates with the relative potency of the drug, dosage, timing of
administration and duration of treatment (see Special warnings and special
precautions for use).
PARENTERAL CORTICOSTEROID THERAPY - Anaphylactic reaction or
allergic reactions, hypopigmentation or hyperpigmentation, subcutaneous and
cutaneous atrophy, sterile abscess, post injection flare (following intraarticular use), Charcot-like arthropathy, rare instances of blindness associated
with intralesional therapy around the face and head.
GASTRO-INTESTINAL - Dyspepsia, peptic ulceration with perforation and
haemorrhage, abdominal distension, oesophageal ulceration, oesophageal
candidiasis, acute pancreatitis, perforation of bowel.
Increases in alanine transaminase (ALT, SGPT) aspartate transaminase (AST,
SGOT) and alkaline phosphatase have been observed following corticosteroid
treatment. These changes are usually small, not associated with any clinical
syndrome and are reversible upon discontinuation.
ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE EFFECTS Increased susceptibility and severity of infections with suppression of clinical
symptoms and signs, opportunistic infections, may suppress reactions to skin
tests, recurrence of dormant tuberculosis (see Special warnings and special
precautions for use).
MUSCULOSKELETAL - Proximal myopathy, osteoporosis, vertebral and
long bone fractures, avascular osteonecrosis, tendon rupture, aseptic necrosis,
muscle weakness.

FLUID AND ELECTROLYTE DISTURBANCE - Sodium and water
retention, potassium loss, hypertension, hypokalaemic alkalosis, congestive
heart failure in susceptible patients.
DERMATOLOGICAL - Impaired healing, petechiae and ecchymosis, thin
fragile skin, skin atrophy, bruising, striae, telangiectasia, acne.
ENDOCRINE/METABOLIC - Suppression of the hypothalamo-pituitaryadrenal axis, growth suppression in infancy, childhood and adolescence,
menstrual irregularity and amenorrhoea. Cushingoid facies, hirsutism, weight
gain, impaired carbohydrate tolerance with increased requirement for
antidiabetic therapy, negative nitrogen and calcium balance. Increased
appetite.
NEUROPSYCHIATRIC - A wide range of psychiatric reactions including
affective disorders (such as irritable, euphoric, depressed and labile mood
psychological dependence and suicidal thoughts), psychotic reactions
(including mania, delusions, hallucinations and aggravation of schizophrenia),
behavioural disturbances, irritability, anxiety, sleep disturbances and cognitive
dysfunction including confusion and amnesia have been reported for all
corticosteroids. Reactions are common and may occur in both adults and
children. In adults, the frequency of severe reactions was estimated to be 56%. Psychological effects have been reported on withdrawal of
corticosteroids; the frequency is unknown. Increased intra-cranial pressure
with papilloedema in children (pseudotumour cerebri) has been reported,
usually after treatment withdrawal of methylprednisolone.

OPHTHALMIC - Increased intra-ocular pressure, glaucoma, papilloedema,
cataracts with possible damage to the optic nerve, corneal or scleral thinning,
exacerbation of ophthalmic viral or fungal disease, exophthalmos.
GENERAL - Leucocytosis, hypersensitivity including anaphylaxis, thromboembolism, nausea, vertigo.
WITHDRAWAL SYMPTOMS - Too rapid a reduction of corticosteroid
dosage following prolonged treatment can lead to acute adrenal insufficiency,
hypotension and death. However, this is more applicable to corticosteroids
with an indication where continuous therapy is given (see Special warnings
and special precautions for use).
A 'withdrawal syndrome' may also occur including, fever, myalgia, arthralgia,
rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.
CERTAIN
SIDE-EFFECTS
REPORTED WITH
RECOMMENDED ROUTES OF ADMINISTRATION.

SOME

NON-

Intrathecal:
Usual systemic corticoid adverse reactions, headache,
meningismus, meningitis, paraplegia, spinal fluid abnormalities, nausea,
vomiting, sweating, arachnoiditis, convulsions.

Extradural: Wound dehiscence, loss of sphincter control.
Intranasal: Permanent/temporary blindness, rhinitis.
Ophthalmic: (Subconjunctival) - Redness and itching, abscess, slough at
injection site, residue at injection site, increased intra-ocular pressure,
decreased vision - blindness, infection.
Miscellaneous injection sites - Scalp, tonsillar fauces, sphenopalatine
ganglion: blindness.

4.9

Overdose
There is no clinical syndrome of acute overdosage with Depo-Medrone.
Following overdosage the possibility of adrenal suppression should be
guarded against by gradual diminution of dose levels over a period of time. In
such event the patient may require to be supported during any further
traumatic episode.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Methylprednisolone acetate is a synthetic glucocorticoid. It has greater antiinflammatory potency than prednisolone and less tendency than prednisolone to
induce sodium and water retention. An aqueous suspension may be injected directly
into joints and soft tissues in the treatment of rheumatoid arthritis, osteoarthritis,
bursitis and similar inflammatory conditions. For prolonged systemic effect it may be
administered intramuscularly.

5.2

Pharmacokinetic properties
Absorption:
One in-house study of eight volunteers determined the pharmacokinetics of a
single 40 mg intramuscular dose of Depo-Medrone. The average of the
individual peak plasma concentrations was 14.8 ± 8.6 ng/mL, the average of
the individual peak times was 7.25 ± 1.04 hours, and the average area under
the curve (AUC) was 1354.2 ± 424.1 ng/mL x hrs (Day 1-21).
Distribution:
Methylprednisolone is widely distributed into the tissues, crosses the bloodbrain barrier, and is secreted in breast milk. Its apparent volume of distribution
is approximately 1.4 L/kg. The plasma protein binding of methylprednisolone
in humans is approximately 77%.

Metabolism:
In humans, methylprednisolone is metabolized in the liver to inactive
metabolites; the major ones are 20α-hydroxymethylprednisolone and 20βhydroxymethylprednisolone. Metabolism in the liver occurs primarily via the
CYP3A4. (For a list of drug interactions based on CYP3A4-mediated
metabolism, see section 4.5 Interactions with Other Medicinal Products and
Other Forms of Interaction.)
Methylprednisolone, like many CYP3A4 substrates, may also be a substrate
for the ATP-binding cassette (ABC) transport protein p-glycoprotein,
influencing tissue distribution and interactions with other medicines.
Elimination:
The mean elimination half-life for total methylprednisolone is in the range of
1.8 to 5.2 hours. Total clearance is approximately 5 to 6 mL/min/kg.
No dosing adjustments are necessary in renal failure. Methylprednisolone is
haemodialysable.
Methylprednisolone acetate is less soluble than methylprednisolone.
5.3

Preclinical safety data
Based on conventional studies of safety pharmacology and repeated dose
toxicity, no unexpected hazards were identified. The toxicities seen in
repeated-dose studies were those expected to occur with continued exposure to
exogenous adrenocortical steroids.
There was no evidence of a potential for genetic and chromosome mutations in
limited studies performed in bacteria and mammalian cells. Long-term studies
in animals have not been performed to evaluate carcinogenic potential, as the
drug is indicated for short-term treatment only.
Corticosteroids have been shown to be teratogenic in many species when
given in doses equivalent to the human dose. In animal reproduction studies,
glucocorticoids such as methylprednisolone have been shown to induce
malformations (cleft palate, skeletal malformations) and intra-uterine growth
retardation.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Polyethylene glycol, sodium chloride, myristyl-gamma-picolinium chloride
and sterile water for injections.

6.2

Incompatibilities
None stated.

6.3

Shelf life
Shelf-life of the medicinal product as packaged for sale: 60 months.
Depo-Medrone should not be mixed with any other fluid.
remaining suspension after use.

Discard any

6.4

Special precautions for storage
Depo-Medrone should be protected from freezing.

6.5

Nature and contents of container
Type I flint glass vial with a butyl rubber plug and metal seal. Each vial
contains 1 ml, 2ml, or 3 ml of Depo-Medrone 40 mg/ml.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
Pfizer Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 00057/0963

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of first authorisation: 07/03/1989.

Last renewal date: 05/09/1996.

10

DATE OF REVISION OF THE TEXT
30/08/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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